The overall objective of our research is improved understanding of the immunobiology of the gastrointestinal tract and relationships between gut immunobiology and chronic intestinal diseases such as the inflammatory bowel diseases and carcinoma. The specific aims of this proposal are to: 1) Evaluate the secretory component (SC) in human and experimental colorectal tumors, and 2) Evaluate the role of SC in the transepithelial translocation of immunoglobulins, using cultured human colonic cancer cells as a source of SC-bearing cells. With respect to the first aim, SC is a well-characterized glycoprotein product of epithelial cells that is a marker of epithelial cell differentiation in the colon. Its absence from colonic epithelium may be an early sign of malignancy. Therefore, we propose to study by immunocytochemical techniques the SC in chemically induced carcinoma in rats and in human colorectal tumors. We will try to determine if SC is altered in colonic malignancies and, if so, whether these alterations are early and diagnostically useful signs of malignant transformation of colonic epithelial cells. With respect to the second aim, SC may be important in the transepithelial transport of IgA and IgM into the intestinal lumen, perhaps by serving as receptor on epithelial cells for these immunoglobulins. Because IgA and IgM antibodies may play a role in protecting the gut mucosa, understanding their transepithelial transport is important. Long term cultures of certain human colonic cancer cells synthesize SC. We propose to use these SC-bearing cells to determine the role of SC in the binding, uptake, assembly and intracellular transit of immunoglobulins by gut epithelial cells.